Tumoricidal activity of pristimerin versus human myeloma xenografts in mice. Human myeloma cells from RPMI-8226 or OCI-MY5 cultures were implanted subcutaneously in the right flank of beige nude (BNX) mice in 50% (vol/vol) Matrigel matrix and tumors were allowed to establish over approximately 2 weeks. In initial testing, single paired mice with (A) 8226 or (B) MY5 xenografts were treated with daily subcutaneous pristimerin 2.5 mg/kg per day in a depot formulation, or with vehicle, and tumor size was monitored. Although an antitumor effect appeared likely, mice treated with subcutaneous pristimerin developed delayed injection site necrosis, requiring cessation of therapy and euthanasia. (C) Repeat efficacy studies, using xenografted BNX mice (n = 4/group) treated with systemic liposomal pristimerin or vehicle, delivered via tail vein injection, at doses escalating from 0.25 mg/kg per dose to 2.5 mg/kg per dose, administered 2 to 3 times weekly, commenced after mean tumor volumes exceeded 70 mm.3 P value was calculated by paired t test. No cutaneous side effects were observed with systemic liposomal pristimerin.
